Table 3.
Summary of results of papers included in review (n=20), stratified by anticholinergic burden (ACB) measure.
| Study | Cohort size (N) | Design | Setting | F/up (months) | Unadjusted Results – HR/OR (95%CI) | Adjusted Results – HR/OR (95%CI) |
|---|---|---|---|---|---|---|
| ACBS | ||||||
| Chatterjee et al. (2017) | 224,740 | Nested case control | Current and former nursing home residents | 60 and 90 days prior to death | NR | ACBS level 2/3, prescribed within 90 days: OR 1.24 (1.21, 1.27)a |
| Cross et al. (2017) | 964 | Retrospective cohort | Patients attending memory clinics | 36 months and 90 days | Baseline ACBS score HR 1.27 (1.15-1.40) | Baseline ACBS score: HR 1.15 (1.01-1.31)b |
| ACBS score over study period HR 1.29 (1.19-1.39) | ACBS score over study period: HR 1.18 (1.06-1.32)b |
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| Egberts et al. (2017) | 905 | Retrospective cohort | Geriatric ward admissions | Up to discharge (median 8 days, IQR 5-11) | NR | Low (1-2): OR 1.52 (0.79–2.93)c |
| High (≥3): OR 1.47 (0.66–3.25)c | ||||||
| Fox et al. (2011) | 12,423 | Prospective cohort | Community-dwelling and institutionalised older persons | 24 | NR | Continuous: OR 1.26 (1.20–1.32)d |
| Low (≥1): OR 1.56 (1.36–1.79)d | ||||||
| High (≥2): OR 1.68 (1.30–2.16)d | ||||||
| Kidd et al. (2014) | 419 | Prospective cohort | Acute medical assessment units or acute geriatric ward | In-hospital mortality – 3 day, 7 day and overall | Overall mortality: 1: OR 1.04 (0.58–1.86) |
Overall mortality: Low (1): OR 1.01 (0.53–1.95)f |
| ≥2: OR 1.10 (0.60–2.04) | High (≥2): OR 1.23 (0.58–2.63)f | |||||
| Lattanzio et al. (2018a) | 807 | Prospective cohort | Patients discharged from acute geriatric care wards | 12 | NR | Low (1): HR 1.19 (0.75–1.90)i |
| High (≥2): HR 1.69 (1.09–2.65)i | ||||||
| Adjusted for ACBS at 3-month follow-up: HR 1.33 (0.97–2.05)i |
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| Lattanzio et al. (2018b) | 807 | Prospective cohort | Patients discharged from acute geriatric care wards | 12 | NR | No BADL dependency (n = 537) Low (1): HR 0.92 (0.45–1.89)j High (≥2): HR 1.06 (0.50–2.34)j Continuous: HR 0.98 (0.75–1.28)j |
| Dependency in ≥ 1 BADL (n= 270) Low (1): HR 1.50 (0.81-2.73)j High (≥2): HR 2.25 (1.22–4.14)j Continuous: HR 1.28 (1.11–1.49)j |
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| Adjusted for ACBS at 3-month follow-up (with BADL dependency) High (≥2): HR 2.18 (1.20–3.98)j |
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| Mangoni et al. (2013) | 71 | Prospective cohort | Patients admitted with hip fractures and scheduled for surgery | 3 and 12 | Univariate analysis of 3-month mortality Continuous: HR 1.1 (0.7–1.8) |
NR |
| Univariate analysis of 1-year mortality Continuous: HR 1.1 (0.7–1.8) |
NR | |||||
| Mangoni et al. (2013) | 3,761 | Retrospective cohort | Nursing homes | 60 | NR | Low (1): HR 1.46 (1.12–1.9)p |
| High (≥2): HR 1.41 (1.11–1.79)p | ||||||
| ADS | ||||||
| Chatterjee et al. (2017) | 224,740 | Nested case control | Current and former nursing home residents | 60 and 90 days prior to death | ADS level 2/3 (high), prescribed within 90 days: OR 1.37(1.34, 1.40)a |
|
| Mangoni et al. (2013) | 71 | Prospective cohort | Patients admitted with hip fractures and scheduled for surgery | 3 and 12 | Univariate analysis of 3-month mortality HR 1.3 (0.9–1.9) |
NR |
| Univariate analysis of 1-year mortality HR 1.2 (0.9–1.6) |
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| Sarbacker et al. (2017) | 1,497 | Prospective cohort | Hispanic Established Populations for the Epidemiologic Study of the Elderly | 108 (9 years) | HR 1.12 (1.07–1.17) | Continuous: HR 1.09 (1.04–1.15)n |
| Sevilla-Sánchez et al. (2018) | 235 | Prospective cohort | Acute care geriatric unit | 12 | NR | Continuous: HR 1.54 (0.74–3.18)o |
| High (> 3) vs low (< 3) use: HR 1.05 (0.75–1.47)o |
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| ARS | ||||||
| Aalto et al. (2018) | 2,432 | Prospective cohort | Nursing homes and assissted living facilties | 12 | No. of deaths during 1 year follow up (%) p value: 0.11 |
NR |
| 0 DAPs: 238 (20%) | ||||||
| 1 DAP: 134 (20%) | ||||||
| 2 DAPs: 56 (18%) | ||||||
| 3+ DAPs: 50 (20%) | ||||||
| Egberts et al. (2017) | 905 | Retrospective cohort | Geriatric ward admissions | Up to discharge (median 8 days, 5–11 IQR) | NR | Low (1-2): OR 1.2 (0.63–2.27)c |
| High (≥3): OR 1.22 (0.47–3.13)c | ||||||
| Gutiérrez-Valencia et al. (2017) | 921 | Prospective cohort | Patient discharged from geriatric and acute care wards | 12 | 1: 1.68 (1.10, 2.57) | Low (1): 0.96 (0.51, 1.81)e |
| ≥2: 0.87 (0.4, 1.91) | High (≥2): 0.44 (0.12, 1.59)e | |||||
| Kumpula et al. (2011) | 1,004 | Prospective cohort | Long term care wards | 12 | NR | Low (1-2): HR 1.08 (0.84–1.41)g |
| High (≥3): HR 1.05 (0.75–1.46)g | ||||||
| Landi et al. (2014) | 1,490 | Prospective cohort | Nursing homes | 6 and 12 | Continuous: OR 1.02 (0.95–1.17)h | |
| Lowry et al. (2011) | 362 | Prospective cohort | Acute geriatric unit | In-hospital mortality (LOS median 11 days, IQR 4-24) | Continuous: HR 1.31 (0.97–1.77) | Continuous: 1.04 (0.67–1.62)k |
| ARS (dose- adjusted) continuous: 1.43 (0.97-2.12) |
ARS (dose- adjusted) continuous: 1.12 (0.64–1.96)k |
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| Mangoni et al. (2013) | 71 | Prospective cohort | Patients admitted with hip fractures and scheduled for surgery | 3 and 12 | Univariate analysis of 3-month mortality Continuous: HR 1.6 (1.2–2.2) |
Multivariate 3-month mortality Continuous: HR 2.2 (1.2-3.7)l |
| Univariate analysis of 1-year mortality Continuous: HR 1.4 (1.1–1.8) |
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| McIsaac et al. (2018) | 245,410 | Retrospective cohort | Noninstitutionalised patients admitted for an elective, major non-cardiac surgery | 90 days | 1-2: HR 1.49 (1.40–1.59) | Low (1-2): HR 1.15 (1.08–1.22)m |
| ≥3: HR 1.39 (1.30–1.49) | High (≥3): HR 1.14 (1.06–1.23)m | |||||
| DBI (anticholinergic) | ||||||
| Lowry et al. (2012) | 362 | Prospective cohort | Acute geriatric unit | In-hospital mortality (LOS median 11 days, IQR 4-24) | Continuous: HR 1.09 (0.46–2.57) | Continuous: HR 1.10 (0.44–2.74)k |
| Mangoni et al. (2013) | 71 | Prospective cohort | Patients admitted with hip fractures and scheduled for surgery | 3 and 12 | Univariate analysis of 3-month mortality Continuous: HR 4.5 (1.2–16.7) |
NR |
| Univariate analysis of 1-year mortality Continuous: HR 3.2 (1.1–9.4) |
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| Miscellaneous scales | ||||||
|
Agar et al. (2010) [Clinician Rated Anti-Cholinergic Scale (modified version)] |
112 | Prospective cohort | Southern Adelaide Palliative Care Services - Inpatients and outpatients | Until death (mean survival time: 8.9 weeks (SD 11.6, median 5.3, IQR 0.2-84.4) | “Log-rank data showed no evidence that survival differed significantly between the three groups” | |
|
Egberts et al. (2017) (Chew) |
905 | Prospective cohort | Geriatric ward admissions | Until hospital discharge (LOS median 8 days, IQR 5-11) | NR | Low (0.5–1): OR 1.01 (0.56–1.83)c |
| High (≥1.5): OR 1.39 (0.66–2.92)c | ||||||
|
Gutiérrez-Valencia et al. (2017) (Duran’s list) |
921 | Prospective cohort | Patients discharged from acute and geriatric care wards | 12 | 1: OR 1.84 (1.27, 2.65) | Low (1): OR 1.69 (1.02, 2.82)e |
| ≥2: OR 1.52 (0.86, 2.68) | High (≥2): OR 1.52 (0.86, 2.68)e | |||||
|
Wauters et al. (2017) (MARANTE scale) |
503 | Prospective cohort | General Practitioner centres | 18 | Continuous: HR 1.22 (1.02–1.47) | Continuous: HR 1.09 (0.87–1.36)q |
| Low (0.5–1.5): HR 1.52 (0.68–3.39) | Low (0.5–1.5): HR 1.31 (0.57–3.02)q | |||||
| High (≥2): HR 2.77 (1.43–5.38) | High (≥2): HR 2.20 (1.03–4.67)q | |||||
Papers appear multiple times throughout this table if they have reported their results using more than one ACB measure. “Continuous” denotes when an ACB measure has been used as a continuous variable during analysis. ACBS, Anticholinergic Cognitive Burden Scale; ADS, Anticholinergic Drug Scale; ARS, Anticholinergic Risk Scale; BADL, Basic Activities of Daily Living; DAP(s), Drug(s) with anticholinergic properties; DBI (anticholinergic), anticholinergic component of the Drug Burden Index; HR, Hazard Ratio; IQR, Interquartile Range; LOS, Length of Stay; NR, Not reported; OR, Odds Ratio. Adjustments: aAdjusted for demographic characteristics such as race; co-morbidities such as myocardial infarction, heart failure, vascular diseases, dementia, cerebrovascular events, rheumatological diseases, mild liver disease, pulmonary disorders, renal diseases, ulcer, hemiplegia, diabetes, cancer, metastasis, moderate/chronic liver disease; and duration of depression. bBaseline age, gender, education, dementia/MCI diagnosis, total number of medications, MDBI score, MMSE, SMAF, and NPI score. cAge, sex, Charlson Comorbidity Index (CCI), number of nonanticholinergic drugs and delirium at any time during the hospital stay. dAge, sex, baseline MMSE score, education, social class, number of nonanticholinergic medications, and number of health conditions. eAge, sex, number of chronic diseases, MMSE, impaired ADL and number of non-anticholinergic medications. fAge, no of pre-morbid conditions, ischemic heart disease, no of medications, creatinine and urea. gAdjusted for age, sex, mini nutritional assessment. hAge, gender, comorbidities, baseline functional impairment and cognitive impairment. iAge, sex, cognitive impairment, depression, number of lost BADL, hypertension, heart failure, diabetes, coronary artery disease, atrial fibrillation, peripheral arterial disease, stroke, chronic obstructive pulmonary disease, cancer and number of medications. jAge, sex, cognitive impairment, history of falls, depression, number of medications and hypertension, heart failure, diabetes, coronary artery disease, atrial fibrillation, peripheral arterial disease, stroke, chronic obstructive pulmonary disease, and cancer. kAdjusted for age, sex, institution, dementia, CCI, number of nonanticholinergic drugs, hospital site, Barthel Index category (under 50 vs. 50+). lAge, sex, CCI and preadmission cognitive impairment. mAge, sex, income quartile, comorbidities, one-year mortality risk, total hip replacement (please see paper for extensive list of covariates). nAge, sex, any self-reported diabetes, stroke, smoking, hypertension and cancer. oAge, sex, provenance, age-adjusted CCI, cognitive impairment and geriatric syndromes. pAge, sex, activities of daily living, Depression Rating Scale, Cognitive Performance Scale, dementia, heart failure, stroke, chronic obstructive pulmonary disease, cancer, diabetes, IHD, and hip fracture. qNumber of medications & level of multi-morbidity (0–9).